Next generation brain health: transforming global research and public health to promote prevention of dementia and reduce its risk in young adult populations.

Efforts to prevent dementia can benefit from precision interventions delivered to the right population at the right time; that is, when the potential to reduce risk is the highest. Young adults (aged 18-39 years) are a neglected population in dementia research and policy making despite being highly exposed to several known modifiable risk factors. The risk and protective factors that have the biggest effect on dementia outcomes in young adulthood, and how these associations differ across regions and groups, still remain unclear.

Job satisfaction declines before retirement in Germany.

Job satisfaction has been found to increase with age. However, we still have a very limited understanding of how job satisfaction changes as people approach retirement. This is important as the years before retirement present specific challenges for older workers.

Improving analysis of cognitive outcomes in cardiovascular trials using different statistical approaches.

Background: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials. Because these scales are discrete and bounded with ceiling and floor effects and highly skewed, their analysis as continuous outcomes presents challenges. Normality assumptions of linear regression models are usually violated, which may result in failure to detect associations with variables of interest.

Cardiovascular risk of dementia is associated with brain-behaviour changes in cognitively healthy, middle-aged individuals.

Alzheimer's Disease (AD) neuropathology start decades before clinical manifestations, but whether risk factors are associated with early cognitive and brain changes in midlife remains poorly understood. We examined whether AD risk factors were associated with cognition and functional connectivity (FC) between the Locus Coeruleus (LC) and hippocampus - two key brain structures in AD neuropathology - cross-sectionally and longitudinally in cognitively healthy midlife individuals. Neuropsychological assessments and functional Magnetic Resonance Imaging were obtained at baseline (N=210), and two-years follow-up (N=188).

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant.

The association between selenium status and global and attention-specific cognition in very old adults in the Newcastle 85+ Study: cross-sectional and longitudinal analyses.

Background: Selenium has potential safeguarding properties against cognitive decline, because of its role in protecting DNA, proteins, and lipids in the brain from oxidative damage. However, acute and chronic overexposure to selenium can be neurotoxic.

Objective: The aim of this analysis was to explore the association between selenium status [serum selenium and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity] and cognitive function in 85-y olds living in Northeast England at baseline and ≤5 y of follow-up.

Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study.

Importance: Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.

Objective: To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.

Association of optic disc pallor and RNFL thickness with cerebral small vessel disease in the PREVENT-Dementia study.

Introduction: We tested associations between two retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer [pRNFL] thickness) and four magnetic resonance imaging markers of cerebral small vessel disease (SVD; lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces [ePVSs]).

Methods: We used PallorMetrics to quantify optic disc pallor from fundus photographs, and pRNFL thickness from optical coherence tomography scans. Linear and logistic regression assessed relationships between retinal measures and SVD markers.

Texture-based morphometry in relation to apolipoprotein ε4 genotype, ageing and sex in a midlife population.

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle-aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non-carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification.

The Flynn effect and cognitive decline among americans aged 65 years and older.

To contribute to our understanding of cohort differences and the Flynn effect in the cognitive decline among older Americans, this study aims to compare rates of cognitive decline between two birth cohorts within a study of older Americans and to examine the importance of medical and demographic confounders. Analyses used data from the National Health and Aging Trends Study (2011-2019), which recruited older Americans in 2011 and again in 2015 who were then followed for 5 years. We employed mixed-effect models to examine the linear and quadratic main and interaction effects of year of birth while adjusting for covariates such as annual round, sex/gender, education, race/ethnicity, heart disease, hypertension, diabetes, test unfamiliarity, and survey design.

Older caregivers' depressive symptomatology over time: evidence from the Survey of Health, Ageing and Retirement in Europe.

The prevalence of informal caregiving is increasing as populations across the world age. Caregiving has been found to be associated with poor mental health outcomes including depressive symptoms. The purpose of this study is to examine the mean trajectory of depressive symptomatology in older caregivers in a large European sample over an eight-year period, the effects of time-varying and time-invariant covariates on this trajectory, and the mean trajectory of depressive symptomatology according to pattern of caregiving.

Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study.

Background: Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates has not been quantified.

Healthy lifestyle and cognitive decline in middle-aged and older adults residing in 14 European countries.

Studies examining lifestyle and cognitive decline often use healthy lifestyle indices, making it difficult to understand implications for interventions. We examined associations of 16 lifestyles with cognitive decline. Data from 32,033 cognitively-healthy adults aged 50-104 years participating in prospective cohort studies of aging from 14 European countries were used to examine associations of lifestyle with memory and fluency decline over 10 years.

A call for caution when using network methods to study multimorbidity: an illustration using data from the Canadian Longitudinal Study on Aging.

Objectives: To examine the impact of two key choices when conducting a network analysis (clustering methods and measure of association) on the number and type of multimorbidity clusters.

Study Design And Setting: Using cross-sectional self-reported data on 24 diseases from 30,097 community-living adults aged 45-85 from the Canadian Longitudinal Study on Aging, we conducted network analyses using 5 clustering methods and 11 association measures commonly used in multimorbidity studies. We compared the similarity among clusters using the adjusted Rand index (ARI); an ARI of 0 is equivalent to the diseases being randomly assigned to clusters, and 1 indicates perfect agreement.

Towards a lifelong personalized brain health program: empowering individuals to define, pursue, and monitor meaningful outcomes.

Incorporating person-centered outcomes into clinical trials for neurodegenerative diseases has been challenging due to a deficiency in quantitative measures. Meanwhile, the integration of personally meaningful treatment targets in clinical practice remains qualitative, failing to truly inform evaluations, therapeutic interventions and longitudinal monitoring and support. We discuss the current advances and future directions in capturing individualized brain health outcomes and present an approach to integrate person-centered outcome in a scalable manner.

The PREVENT dementia programme: baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia.

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort.

The Mediterranean diet is not associated with neuroimaging or cognition in middle-aged adults: a cross-sectional analysis of the PREVENT dementia programme.

Background And Purpose: The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin.

Methods: This study used data from the PREVENT dementia programme.

PallorMetrics: Software for Automatically Quantifying Optic Disc Pallor in Fundus Photographs, and Associations With Peripapillary RNFL Thickness.

Purpose: We sough to develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fiber layer (pRNFL) thickness.

Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants.